Influence of the Basal Ganglia on Cerebellar Action

描述（由申请人提供）： 成像和微电子技术的进步使神经外科医生能够识别大脑的小区域，并植入电极来激活这些区域的细胞。脑深部电刺激（DBS）被证明是一种令人惊讶的有效方法，用于控制与基底神经节疾病（如帕金森病）相关的运动障碍。在帕金森病患者中，DBS可以消除或减少震颤、运动不能和药物引起的运动障碍。这些运动障碍在疾病的晚期通常完全致残。最近的多组研究表明，DBS可以为帕金森病患者提供有效的症状缓解，持续数年。然而，DBS的使用还处于起步阶段，没有人知道刺激适当的大脑区域以实现最佳的行为改善。 我们研究的目的是了解神经系统如何控制肢体运动。我们特别感兴趣的是表征大脑中控制肢体在达到抓住一个物体。帕金森病患者在启动和执行伸手抓握时遇到困难，但可以通过刺激或破坏基底神经节的特定区域来改善运动。我们相信，来自基底神经节的输出干扰了接受小脑输入的脑干运动核团的正常运作。我们的研究已经确定了猫的几个脑干区域整合基底神经节和小脑输出。我们的同事已经将这些发现应用于指导人类DBS，并有效缓解了与帕金森病和多发性硬化症相关的运动症状。拟议的研究将使用猫作为受试者：1）识别和表征基底神经节输出核中在伸手抓握期间放电的细胞。2)确定这些细胞的重要性，达到和抓住暂时失活或刺激它们与化学物质和记录的影响运动。3)通过注射6-OHDA破坏多巴胺能细胞建立单侧帕金森病模型。4)尝试通过灭活或激活脑干的特定区域来使6-OHDA模型中的肢体运动正常化。这些数据将帮助我们了解DBS的工作原理，并确定DBS治疗运动障碍的候选区域。

DESCRIPTION (provided by applicant): Advances in imaging and micro-electronics now enable neurosurgeons to identify small regions of the brain and implant electrodes to activate cells in those regions. Deep brain stimulation (DBS) is proving to be a surprisingly effective approach for the control of movement disorders associated with diseases of the basal ganglia, such as Parkinson's disease. In Parkinson's patients, DBS can eliminate or reduce tremor, akinesia and drug-induced dyskinesias. These motor disorders are often totally disabling in advanced stages of the disease. Recent multi-group studies have demonstrated that DBS can provide effective symptomatic relief to Parkinson patients for periods extending over several years. However, the use of DBS is in its infancy, and no one knows the appropriate brain regions to stimulate to achieve optimal behavioral improvement. The goal of our research is to understand how the nervous system controls limb movements. We are particularly interested in characterizing regions of the brain that control the limb during reaching to grasp an object. Parkinson's patients experience difficulty in initiating and performing the reach-to-grasp, but the movement can be improved by stimulating or destroying specific regions of the basal ganglia. We believe that output from the basal ganglia interferes with normal operation of brainstem motor nuclei that receive input from the cerebellum. Our research has identified several brainstem regions of the cat that integrate basal ganglia and cerebellar output. Our colleagues have applied these findings to guide DBS in the human and have produced effective relief of motor symptoms related to Parkinson's disease and multiple sclerosis. The proposed studies will use cats as subjects to: 1) Identify and characterize cells in the basal ganglia output nuclei that discharge during reaching to grasp. 2) Determine the importance of these cells for reaching and grasping by temporarily inactivating or stimulating them with chemical substances and recording effects on movement. 3) Develop a unilateral model of Parkinson's disease by destroying dopaminergic cells with injections of 6-OHDA. 4) Attempt to normalize limb movements in the 6-OHDA model by inactivating or activating specific regions of the brainstem. The data will help us understand how DBS works and will identify candidate regions for the use of DBS in the treatment of motor disorders.